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Investigation of Androgen Receptor Signaling Pathways with Epigenetic Machinery in Prostate Cancer

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Molecular Oncology: Underlying Mechanisms and Translational Advancements

Abstract

Androgen receptor (AR) is a ligand-dependent transcription factor reportedly involved in regulation of wide ranging target genes. Rapidly emerging experimental evidence has provided detailed information related to 3D crystal structures of the ligand binding domain (LBD) and DNA binding domain (DBD) of AR.

Targeting of AR induced signaling cascade is assumed to be effective for treating castration-resistant prostate cancer (CRPC), which possesses resistance to the general anti-androgen therapy. The aggressiveness of cancer cells is induced by the interplay of multiple signal pathways, transcription factors and epigenetic machinery. To investigate how AR modulates transcriptional networks in prostate cancer cells, global analyses determining AR binding sites and androgen-regulated transcripts including coding and non-coding genes have been performed. In addition, diverse regulations of epigenetics such as histone modification and DNA methylation were found to be linked with the activation and repression of enhancers and promoters with AR recruitments. These regulatory mechanisms are interconnected strongly and regulate the gene expression in prostate cancer cells. In recent studies, many androgen-regulated genes have been shown to have important roles in the development of prostate cancer and clinical relevance as new biomarkers and therapy targets. In this chapter, we highlight those epigenetic mechanisms for AR activation by various factors, especially long non-coding RNA (lncRNA) and microRNA (miRNA). We also describe the molecular mechanism through which AR downstream signals induce tumor growth and inhibit apoptosis for developing CRPC.

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Authors and Affiliations

  1. Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan

    Ken-ichi Takayama & Satoshi Inoue

  2. Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, 350-1241, Japan

    Satoshi Inoue

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  1. Ken-ichi Takayama
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Correspondence to Satoshi Inoue .

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Editors and Affiliations

  1. Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan

    Ammad Ahmad Farooqi

  2. Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan

    Muhammad Ismail

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Takayama, Ki., Inoue, S. (2017). Investigation of Androgen Receptor Signaling Pathways with Epigenetic Machinery in Prostate Cancer. In: Farooqi, A., Ismail, M. (eds) Molecular Oncology: Underlying Mechanisms and Translational Advancements. Springer, Cham. https://doi.org/10.1007/978-3-319-53082-6_10

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